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Permanent link (DOI): https://doi.org/10.7939/R3P69J

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NEUTROPHIL SECRETION OF THE PROINFLAMMATORY CYTOKINE TNF VIA RECYCLING ENDOSOMES Open Access

Descriptions

Other title
Subject/Keyword
Recycling endosomes
TNF
Neutrophil
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Srivastava, Nutan
Supervisor and department
Dr. Paige lacy
Examining committee member and department
Dr. Paige Lacy (Department of Medicine)
Dr. Joel Dacks (Department of Cell Biology)
Dr. Allan Murray (Department of Medicine)
Dr. Michael Sean McMurtry (Department of Medicine)
Dr. Gary Eitzen (Department of Cell Biology)
Department
Department of Medicine
Specialization

Date accepted
2015-01-30T11:34:49Z
Graduation date
2015-06
Degree
Master of Science
Degree level
Master's
Abstract
Neutrophils are highly abundant innate immune cells that are important in immediate responses to injury and infection, and secrete the proinflammatory cytokine tumor necrosis factor (TNF). Inflammatory cytokines have many potent effects and their excess or deficiency may have many clinical consequences. However, cytokine trafficking and secretion in neutrophils has not been well characterized. Recycling endosomes (REs) are specialized secretory compartments that perform multiple functions including trafficking of cytokines to cell surfaces, although these are not characterized in neutrophils. Our objective is to identify trafficking components in neutrophils that may contribute to cytokine secretion. This study presents data that shows that LPS induced 30-40% TNF secretion from stored sources, with the remainder newly synthesized. We also found that neutrophils possess REs as determined by transferrin uptake and VAMP-3 labeling. TNF also colocalized with REs, primary and secondary granules as well as early and late endosomes, suggesting multiple sites of TNF storage and trafficking in neutrophils. TNF colocalized with VAMP-3 around periphery of cells after 1 h stimulation with LPS, suggesting TLR4-induced TNF trafficking via REs. The present study provides evidence that movement of TNF+VAMP-3+ vesicles towards the cell periphery in response to LPS. This suggests that neutrophils utilize REs for trafficking of TNF to the cell surface in response to TLR4 signaling. These findings contribute to our understanding of how neutrophils package, transport, and release cytokines.
Language
English
DOI
doi:10.7939/R3P69J
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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